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SKRIPSI
NUR AFNI FITHRIYAH
STUDI PENGGUNAAN OBAT ANTI
TUBERKULOSIS PASIEN BARU BTA POSITIF
PADA TAHAP INTENSIF
(Penelitian dilakukan di Poli Directly Observed Treatment
Short-course dan Rekam Medik Kesehatan RSU Karsa
Husada Batu)
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG
2017
ii
iii
iv
KATA PENGANTAR
Assalamualaikum Wr. Wb.
Puji syukur kehadirat Allah SWT yang telah melimpahkan berkah dan nikmat
kepada hamba-Nya, karena dengan pertolongan-Nya skripsi yang berjudul “Studi
Penggunaan Obat Anti Tuberkulosis Pasien Baru BTA Positif pada Tahap Intensif
(Penelitian dilakukan di Poli Directly Observed Treatment Short-course dan
Rekam Medik Kesehatan RSU Karsa Husada Batu)” dapat diselesaikan tepat
waktu dan dengan sebaik-baiknya.
Selanjutnya penulis ingin mengucapkan terima kasih yang tidak terhingga kepada
orang tua Bapak serta Ibu karena telah senantiasa untuk selalu mendoakan dan
memberi semangat, selalu memberikan kebutuhan yang diperlukan dan selalu
sabar dalam memahami keinginanan penulis. Terima kasih juga kepada:
1. Bapak Yoyok Bekti Prasetyo, S.Kep., M.Kep., Sp.Kom. selaku dekan
Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang.
2. Direktur dan staf RSU Karsa Husada Batu yang telah membantu
kelancaran penelitian skripsi.
3. Ibu Hidajah Rachmawati, S.Si, Apt., Sp.FRS selaku pembimbing I yang
selalu sabar dalam memberikan saran dan kritikan yang membangun
hingga tugas akhir ini dapat diselesaikan tepat waktu, semoga Allah
selalu melimpahkan kesehatan.
4. Bapak Drs. Didik Hasmono, Apt., M.S. selaku pembimbing II yang telah
banyak meluangkan waktu untuk membimbing, mengarahkan dan
memberi semangat kepada penulis selama menempuh pendidikan di
program studi farmasi Universitas Muhammadiyah Malang sampai
terselesaikannya tugas akhir ini, semoga Allah selalu melimpahkan
kesehatan.
5. Ibu Dra. Lilik Yusetyani, Apt., Sp.FRS. dan Ibu Nailis Syifa’, S.Farm.,
M.Sc., Apt. selaku penguji I dan II yang telah banyak memberikan
masukan dan saran demi terselesaikannya tugas akhir ini dengan sebaik-
baiknya.
v
vi
RINGKASAN
STUDI PENGGUNAAN OBAT ANTI TUBERKULOSIS PASIEN BARU
BTA POSITIF PADA TAHAP INTENSIF
(Penelitian dilakukan di Poli Directly Observed Treatment Short-course dan
Rekam Medik Kesehatan RSU Karsa Husada Batu)
Tuberculosis (TB) adalah penyakit yang disebabkan oleh bakteri
Mycobacterium tuberculosis yang paling sering menyerang paru-paru (TB Paru)
dan beberapa bagian tubuh lain (TB Ekstra Paru). Tuberkulosis merupakan
peringkat ke-10 penyakit yang mematikan di dunia. Indonesia merupakan negara
yang memiliki angka insidensi TB tertinggi kasus baru dengan BTA+ sebanyak
176.677 kasus. Penularan terjadi ketika seseorang menghirup “droplet nuclei”
yang mengandung Mycobacterium tuberculosis dan masuk melalui mulut atau
hidung, saluran pernapasan bagian atas dan bronkus hingga mencapai alveoli
paru-paru. Gejala utama pasien TB paru adalah batuk berdahak yang diikuti
dengan gejala tambahan yaitu dahak bercampur darah, batuk darah, sesak nafas,
badan lemas, nafsu makan menurun, berat badan menurun, malaise, berkeringat
malam hari tanpa kegiatan fisik, dan demam. Pengobatan pada penderita TB
diberikan sesuai dengan kategori pasien. Kategori pasien diklasifikasikan atas tiga
kategori yaitu kategori 1 (pasien baru dengan TB paru BTA positif, hasil biakan
Mycobacterium tuberculosis positif, hasil tes cepat Mycobacterium tuberculosis
positif, pasien TB anak yang terdiagnosis dengan pemeriksaan bakteriologis, BTA
negatif dengan foto toraks positif dan pasien ekstraparu), kategori 2 (pasien
kambuh, gagal pengobatan dan pasien putus berobat) serta kategori anak. Obat
Anti Tuberkulosis (OAT) adalah komponen terpenting dalam pengobatan TB
yang diberikan untuk mencegah penyebaran lebih lanjut dari kuman TB.
Pemberian OAT diberikan dalam dua tahap yaitu tahap intensif (2-3 bulan) yang
diberikan setiap hari serta tahap lanjutan (4-7 bulan). Tahap intensif dimaksudkan
untuk menurunkan jumlah kuman yang ada dalam tubuh pasien secara efektif,
mencegah penularan sedangkan pada tahap lanjutan dimaksudkan untuk
mencegah kekambuhan. OAT yang sering dipakai adalah rifampisin (R), isoniazid
(H), prazinamid (Z), etambutol (E) dan streptomisin (S) sebagai obat lini pertama.
Terapi pada pasien baru dengan BTA positif disesuaikan dengan kategori yang
direkomendasikan oleh Depkes RI yaitu kategori 1 (2(HRZE) / 4(HR)3). Tahap
intensif pada dua bulan pertama adalah HRZE yang diberikan setiap hari selama 2
bulan dan kemudian dilanjutkan dengan tahap lanjutan tiga kali dalam seminggu
selama 4 bulan dengan HR.
Tujuan dari penelitian ini yaitu untuk mengetahui pola penggunaan Obat
Anti Tuberkulosis pada pasien baru BTA positif pada tahap intensif yang meliputi
jenis, dosis, rute dan efek samping dengan mengaitkan data klinis maupun data
laboratorium.
Penelitian yang dilakukan bersifat observasional dengan metode deskriptif
retrospektif melalui RMK (Rekam Medis Kesehatan) di Poli Directly Observed
Treatment Short-course dan Rekam Medik Kesehatan RSU Karsa Husada Batu
periode 1 Januari 2015 sampai 31 Desember 2016.
Hasil penelitian diperoleh dari 79 RMK hanya 13 RMK sebagai sampel
yang telah memenuhi kriteria inklusi. Data yang diperoleh dari 13 RMK dapat
vii
diketahui bahwa pola penggunaan OAT meliputi jenis yang sering digunakan
yaitu jenis OAT-KDT sebanyak 13 pasien (100%) dengan dosis 1 x 3 tab 4KDT
(Rifampisin 150 mg, Isoniazid 75 mg, Pirazinamid 400 mg dan Etambutol 275
mg) sebanyak 12 pasien (86%) dan 1 x 4 tab 4KDT (Rifampisin 150 mg,
Isoniazid 75 mg, Pirazinamid 400 mg dan Etambutol 275 mg) sebanyak 2 pasien
(14%). Pola penggunaan OAT tanpa kombinasi dengan antibiotik yaitu 1 x 3 tab
4KDT sebanyak 5 pasien (83%) dan 1 x 4 tab 4KDT sebanyak 1 pasien (17%),
sedangkan OAT kombinasi dengan antibiotik lain yaitu 1 x 4 tab 4KDT dengan
Ceftriaxon (2 x 1 g IV) sebanyak 6 pasien (44%). Pola terapi switching dari OAT
dengan persentase tertinggi yaitu Ceftriaxon (2 x 1 g) IV menjadi Ceftriaxon (2 x
1 g IV) + 1 x 3 tablet 4KDT sebanyak 2 pasien (19%). Efek samping OAT yang
sering muncul yaitu mual sebanyak 4 pasien (25%), muntah sebanyak 3 pasien
(19%) dan peningkatan SGPT/SGOT sebanyak 1 pasien (6%). Kesimpulan dari
penelitian ini yaitu pola penggunaan OAT terkait jenis, dosis, rute telah sesuai
dengan pedoman Depkes RI.
x
DAFTAR ISI
Halaman
HALAMAN JUDUL ................................................................................. i
LEMBAR PENGESAHAN ...................................................................... ii
LEMBAR PENGUJIAN .......................................................................... iii
KATA PENGANTAR................................................................................ iv
RINGKASAN ............................................................................................ vi
ABSTRAK ................................................................................................. viii
ABSTRACT ............................................................................................... ix
DAFTAR ISI .............................................................................................. x
DAFTAR TABEL ..................................................................................... xv
DAFTAR GAMBAR ................................................................................. xvi
DAFTAR LAMPIRAN ............................................................................. xvii
DAFTAR SINGKATAN .......................................................................... xviii
BAB I PENDAHULUAN
1.1 Latar Belakang .................................................................. 1
1.2 Rumusan Masalah ............................................................. 4
1.3 Tujuan Penelitian .............................................................. 4
1.3.1 Tujuan Umum ....................................................... 4
1.3.2 Tujuan Khusus ....................................................... 4
1.4 Manfaat Penelitian ............................................................ 5
BAB II TINJAUAN PUSTAKA
2.1 Anatomi Paru .................................................................... 6
2.2 Definisi Tuberkulosis ........................................................ 8
2.3 Epidemiologi Tuberkulosis ............................................... 8
2.4 Etiologi Tuberkulosis ........................................................ 10
2.5 Patogenesis Tuberkulosis .................................................. 12
2.6 Klasifikasi Tuberkulosis.................................................... 13
2.6.1 Berdasarkan definisi TB ........................................ 13
xi
2.6.1.1 Pasien TB terkonfirmasi pemeriksaan
Bakteriologis............................. .............. 13
2.6.1.2 Pasien TB terdiagnosis secara Klinis....... 13
2.6.2 Berdasarkan lokasi anatomi dari penyakit............. 14
2.6.2.1 Tuberkulosis Paru ................................... 14
2.6.2.2 Tuberkulosis Esktra Paru ........................ 14
2.6.3 Berdasarkan riwayat pengobatan sebelumnya ...... 14
2.6.3.1 Pasien Baru............................................. 14
2.6.3.2 Pasien Kambuh ....................................... 14
2.6.3.3 Pasien Gagal.................................... ........ 14
2.6.3.4 Pasien Putus Berobat......................... ...... 14
2.6.3.5 Pasien tidak diketahui riwayat pengobatan
sebelumnya............................................. . 15
2.6.4 Berdasarkan hasil pemeriksaan uji kepekaan obat 15
2.6.4.1 Mono Resisten........................................ . 15
2.6.4.2 Poli Resisten...................................... ...... 15
2.6.4.3 Multi Drug Resisten ................................ 15
2.6.4.4 Extensive Drug Resisten .......................... 15
2.6.4.5 Resisten Rifampisin ................................ 15
2.6.5 Berdasarkan status HIV ......................................... 15
2.6.5.1 TB dengan HIV Positif ........................... 15
2.6.5.2 TB dengan HIV Negatif .......................... 15
2.6.5.3 TB dengan HIV tidak diketahui .............. 15
2.7 Manifestasi Klinis Tuberkulosis ...................................... 16
2.8 Diagnosis Tuberkulosis ..................................................... 16
2.9 Faktor Resiko Tuberkulosis ............................................. 17
2.10 Komplikasi Tuberkulosis .................................................. 18
2.11 Terapi Farmakologi Tuberkulosis...................................... 19
2.11.1 Tahap-Tahap Pemberian OAT .............................. 20
2.11.1.1 Tahap Intensif.......................................... 20
2.11.1.2 Tahap Lanjutan........................................ 21
2.11.2 Kategori Pemberian OAT ...................................... 21
xii
2.11.2.1 Kategori 1...................................... .......... 22
2.11.2.2 Kategori 2...................................... .......... 22
2.11.2.3 Kategori anak...................................... .... 23
2.11.3 Obat Antituberkulosis Lini Pertama ...................... 23
2.11.3.1 Rifampisin ............................................... 24
2.11.3.2 Isoniazid .................................................. 27
2.11.3.3 Pirazinamid ............................................. 28
2.11.3.4 Etambutol ................................................ 30
2.11.3.5 Streptomisin ............................................ 31
2.11.4 Obat Antituberkulosis Lini Kedua ........................ 32
2.11.4.1 Asam Aminosalisilat (PAS) .................... 33
2.11.4.2 Fluoroquinolon ........................................ 34
2.11.4.3 Etionamid ................................................ 36
2.11.4.4 Sikloserin ................................................ 37
2.11.4.5 Kanamisin, Amikasin dan Kapreomisin . 38
2.11.5 Terapi Penunjang pada Tuberkulosis..................... 39
2.11.5.1 Piridoksin (Vitamin B6) .......................... 39
2.11.5.2 Steroid ..................................................... 39
2.11.5.3 Vitamin D ................................................ 39
2.11.6 Terapi Kombinasi Dosis Tetap (KDT) .................. 40
2.12 Terapi Non Farmakologi Tuberkulosis ............................. 41
BAB III KERANGKA KONSEPTUAL dan KERANGKA OPERASIONAL
3.1 Kerangka Konseptual ........................................................ 43
3.2 Kerangka Operasional ....................................................... 44
BAB IV METODE PENELITIAN
4.1 Rancangan Penelitian ........................................................ 45
4.2 Populasi dan Sampel ......................................................... 45
4.2.1 Populasi ................................................................. 45
4.2.2 Sampel ................................................................... 45
4.2.3 Kriteria Data Inklusi .............................................. 45
4.2.4 Kriteria Data Eksklusi ........................................... 46
4.3 Bahan Penelitian................................................................ 46
4.4 Instrumen Penelitian.......................................................... 46
xiii
4.5 Tempat dan Waktu Penelitian ........................................... 46
4.6 Definisi Operasional.......................................................... 46
4.7 Metode Pengumpulan Data ............................................... 47
4.8 Analisis Data ..................................................................... 48
BAB V HASIL PENELITIAN
5.1 Jumlah Sampel Penelitian ................................................. 49
5.2 Karakteristik Demografi Pasien ........................................ 50
5.2.1 Distribusi Usia Pasien Baru BTA Positif pada
Tahap Intensif di RSU Karsa Husada Batu ........... 50
5.2.2 Distribusi Jenis Kelamin Pasien Baru BTA Positif
pada Tahap Intensif di RSU Karsa Husada Batu .. 50
5.2.3 Berat Badan Pasien Baru BTA Positif pada Tahap
Intensif di RSU Karsa Husada Batu ...................... 50
5.2.4 Status Pembiayaan Pasien Baru BTA Positif pada
Tahap Intensif di RSU Karsa Husada Batu ........... 51
5.3 Penyakit Penyerta Pasien Baru BTA Positif pada Tahap
Intensif di RSU Karsa Husada Batu .................................. 51
5.4 Kebiasaan Merokok Pasien Baru BTA Positif pada Tahap
Intensif di RSU Karsa Husada Batu .................................. 51
5.5 Penularan Tuberkulosis Pasien Baru BTA Positif pada
Tahap Intensif di RSU Karsa Husada Batu ....................... 52
5.6 Jenis OAT yang Diterima Pasien Baru BTA Positif pada
Tahap Intensif di RSU Karsa Husada Batu ....................... 52
5.7 Pola Penggunaan OAT Pasien Baru BTA Positif pada
Tahap Intensif di RSU Karsa Husada Batu ....................... 52
5.8 Pola Terapi OAT menggunakan KDT atau KDT Kombinasi
pada Pasien Baru BTA Positif Tahap Intensif di RSU Karsa
Husada Batu ...................................................................... 53
5.9 Pola Switching Rute, Dosis dan Jenis OAT Pasien
Baru BTA Positif pada Tahap Intensif di RSU Karsa
Husada Batu ...................................................................... 54
5.10 Terapi OAT Pasien Baru BTA Positif pada Tahap Intensif
di RSU Karsa Husada Batu Selama MRS ......................... 55
5.11 Efek Samping Terapi OAT Pasien Baru BTA Positif
pada Tahap Intensif di RSU Karsa Husada Batu .............. 55
xiv
5.12 Terapi Lain OAT Pasien Baru BTA Positif pada Tahap
Intensif di RSU Karsa Husada Batu .................................. 56
5.13 Lama MRS Pasien Baru BTA Positif pada Tahap Intensif
di RSU Karsa Husada Batu ............................................... 57
5.14 Keadaan Klinis Pasien Baru BTA Positif pada Tahap
Intensif di RSU Karsa Husada Batu .................................. 58
BAB VI PEMBAHASAN......................................................................... 59
BAB VII KESIMPULAN DAN SARAN
7.1 Kesimpulan ....................................................................... 73
7.2 Saran .................................................................................. 73
DAFTAR PUSTAKA ................................................................................ 75
xv
DAFTAR TABEL
Halaman
Tabel II.1 Kategori Pemberian OAT.............................................. .... .. 21
Tabel II.2 Dosis OAT Kategori 1..................................................... .. .. 22
Tabel II.3 Dosis OAT Kategori 2..................................................... .. .. 23
Tabel II.4 Kisaran Dosis OAT Lini Pertama...................................... .. 23
Tabel II.5 Efek Samping OAT Lini Pertama dan Penatalaksanaan...... 24
Tabel II.6 Dosis OAT Lini Kedua................................................... ... .. 32
Tabel II.7 Farmakokinetik Golongan Floroquinolon....................... .. .. 35
Tabel II.8 Dosis Paduan OAT KDT Kategori 1............................... .. .. 40
Tabel II.9 Dosis Paduan OAT KDT Kategori 2 ................................. .. 41
Tabel V.1 Distribusi Usia Penderita TB................................................ 50
Tabel V.2 Distribusi Jenis Kelamin Penderita TB................................ 50
Tabel V.3 Distribusi Berat Badan Penderita TB................................... 50
Tabel V.4 Distribusi Status Pembiayaan Pengobatan Penderita TB..... 51
Tabel V.5 Penyakit Penyerta Penderita TB........................................... 51
Tabel V.6 Kebiasaan Merokok Penderita TB........................................ 51
Tabel V.7 Kontak Penderita TB pada Pasien Baru BTA Positif ........ .. 52
Tabel V.8 Jenis OAT pada Penderita TB............................... ............ .. 52
Tabel V.9 Pola Penggunaan KDT pada Penderita TB ....................... .. 52
Tabel V.10 Pola terapi OAT baik kombinasi dengan antibiotik lain
atau tidak pada Penderita TB............................................. .. 53
Tabel V.11 Pola Switching Rute, Dosis dan Jenis OAT pada Penderita
TB................................................................................. ..... .. 54
Tabel V.12 Distribusi Lama Pemberian OAT selama MRS pada
Penderita TB..................................................... ................. .. 55
Tabel V.13 Efek Samping pada Penderita TB................................... ... .. 55
Tabel V.14 Terapi Selain OAT pada Penderita TB................................. 56
Tabel V.15 Lama Masuk Rumah Sakit pada Penderita TB.................... 57
Tabel V.16 Keadaan Klinis Ketika KRS pada Penderita TB.................. 58
xvi
DAFTAR GAMBAR
Halaman
Gambar 2.1 Anatomi Paru ....................................................................... 6
Gambar 2.2 Bronkiolus dan Alveoli........................................................ 7
Gambar 2.3 Alveolus dan Respirasi Membran ....................................... 7
Gambar 2.4 Angka Insidensi TB di Dunia .............................................. 9
Gambar 2.5 Angka Insidensi TB dengan HIV ........................................ 9
Gambar 2.6 Kuman TB dan Struktur Dinding Sel Mycobacterium
tuberculosis.......................................................................... 11
Gambar 2.7 Patogenesis Penyakit Tuberkulosis ..................................... 12
Gambar 2.8 Struktur Kimia Rifampisin .................................................. 24
Gambar 2.9 Struktur Kimia Isoniazid ..................................................... 27
Gambar 2.10 Struktur Kimia Pirazinamid ................................................. 28
Gambar 2.11 Struktur Kimia Etambutol ................................................... 30
Gambar 2.12 Struktur Kimi Streptomisin ................................................. 31
Gambar 2.13 Struktur Kimia PAS ............................................................. 33
Gambar 2.14 Struktur Kimia Siprofloksasin dan Moksifloksasin ............ 34
Gambar 2.15 Struktur Kimia Etionamid ................................................... 36
Gambar 2.16 Struktur Kimia Sikloserin .................................................... 37
Gambar 2.17 Struktur Kimia Kapreomisin ............................................... 38
Gambar 3.1 Kerangka Konseptual .......................................................... 43
Gambar 3.2 Kerangka Operasional ......................................................... 44
Gambar 5.1 Skema Jumlah Sampel yang Memenuhi Kriteria Inklusi .... 49
xvii
DAFTAR LAMPIRAN
Halaman
Lampiran 1 Daftar Riwayat Hidup .............................................................. 86
Lampiran 2 Surat Pernyataan ...................................................................... 87
Lampiran 3 Surat Keterangan Selesai Penelitian ........................................ 88
Lampiran 4 Surat Ethical Clearence ........................................................... 89
Lampiran 5 Daftar Nilai Normal Data Klinik dan Data Laboratorium ....... 90
xviii
DAFTAR SINGKATAN
AIDS Acquired Immunodeficiency Syndrome
AMK Amikasin
ARV Anti Retroviral
ATP Adenosin trifosfat
AUC Area Under Curve
BB Berat Badan
BTA Bakteri Tahan Asam
CAP Kapreomisin
CDC Center Disease Control
CNS Central Nervous System
CO2 Karbondioksida
CYP Cytochrome P450
DM Diabetes Mellitus
DNA Deoxyribo Nucleic Acid
DOT Directly Observed Treatment
FDA Food and Drug Administration
G2JPP Gula Darah 2 Jam Post Prandial
GDP Gula Darah Puasa
GDS Gula Darah Sewaktu
GIT Gastrointestinal Tract
Hb Hemoglobin
Hct Hematokrit
HIV Human Immunodeficiency Virus
IFN Interferon
INH Isoniazid
IM Intramuscular
IV Intravena
KAN Kanamisin
KDT Kombinasi Dosis Tetap
KRS Kelur Rumah Sakit
LAM Lipoarabinomannan
xix
LED Laju Endap Darah
LPD Lembar Pengumpul Data
mEq milli equivalent
MDR-TB Multidrug-Resistant Tuberculosis
MIC Minimum Inhibitory Concentration
MRS Masuk Rumah Sakit
O2 Oksigen
OAT Obat Anti Tuberkulosis
PAS para-Amino Salisilat
PGP Polyglycoprotein
PMO Pengawas Menelan Obat
PO Per Oral
PZA Pirazinamid
RIF Rifampisin
RMK Rekam Medik Kesehatan
RNA Ribonucleic Acid
RR Respiration Rate
RS Rumah Sakit Umum
SGOT Serum Glutamic Oxaloacetic Transaminase
SGPT Serum Pyruvic Oxaloacetic Transaminase
SPS Sewaktu Pagi Sewaktu
TB Tuberkulosis
TD Tekanan Darah
WBC White Blood Cell
WHO World Health Organization
75
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